Current Medical Science最新文献

Recent years have seen a burgeoning interest in elucidating the intricate relationship between vestibular dysfunction and sleep disorders, owing to their substantial impact on daily functioning and overall health. Despite significant advancements, the precise mechanisms underpinning this interplay remain elusive. This review aims to synthesize the current literature on the association between vestibular dysfunction and sleep disorders, focusing on potential causal mechanisms and therapeutic implications. We systematically examine various sleep disorders, including insomnia, circadian rhythm disorders, and sleep apnea, in association with specific vestibular dysfunctions, such as Meniere's disease (MD), vestibular migraine (VM), benign paroxysmal positional vertigo (BPPV), vestibular neuritis (VN), and persistent postural perceptual dizziness (PPPD). By exploring these complex interactions, our goal is to provide a comprehensive understanding that contributes to the ongoing discourse in this field. We seek to encourage further investigations into innovative diagnostic and therapeutic strategies, ultimately aiming to improve the clinical management and enhance the quality of life for patients affected by both vestibular dysfunction and sleep disorders.

Objective: This study aimed to develop a prediction model to assess the risk of sepsis-induced coagulopathy (SIC) in sepsis patients.

Methods: We conducted a retrospective study of septic patients admitted to the Intensive Care Units of Shandong Provincial Hospital (Central Campus and East Campus), and Shenxian People's Hospital from January 2019 to September 2024. We used Kaplan-Meier analysis to assess survival outcomes. LASSO regression identified predictive variables, and logistic regression was employed to analyze risk factors for pre-SIC. A nomogram prediction model was developed via R software and evaluated via receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA).

Results: Among 309 patients, 236 were in the training set, and 73 were in the test set. The pre-SIC group had higher mortality (44.8% vs. 21.3%) and disseminated intravascular coagulation (DIC) incidence (56.3% vs. 29.1%) than the non-SIC group. LASSO regression identified lactate, coagulation index, creatinine, and SIC scores as predictors of pre-SIC. The nomogram model demonstrated good calibration, with an AUC of 0.766 in the development cohort and 0.776 in the validation cohort. DCA confirmed the model's clinical utility.

Conclusion: SIC is associated with increased mortality, with pre-SIC further increasing the risk of death. The nomogram-based prediction model provides a reliable tool for early SIC identification, potentially improving sepsis management and outcomes.

Objective: ZW10 interacting kinetochore protein (ZWINT) has been demonstrated to play a pivotal role in the growth, invasion, and migration of cancers. Nevertheless, whether the expression levels of ZWINT are significantly correlated with clinicopathological characteristics and prognostic outcomes of patients with breast cancer remains elusive. This study systematically investigated the clinical significance of ZWINT expression in breast cancer through integrated molecular subtyping and survival analysis.

Methods: We systematically characterized the spatial expression pattern of ZWINT across various breast cancer subtypes and assessed its prognostic significance using an integrated bioinformatics approach that involved multi-omics analysis. The approach included the Breast Cancer Gene-Expression Miner v5.1 (bc-GenExMiner v5.1), TNMplot, MuTarget, PrognoScan database, and Database for Annotation, Visualization, and Integrated Discovery (DAVID).

Results: Our analysis revealed consistent upregulation of ZWINT mRNA and protein expression across distinct clinicopathological subtypes of breast cancer. ZWINT overexpression demonstrated significant co-occurrence with truncating mutations in cadherin 1 (CDH1) and tumor protein p53 (TP53), suggesting potential functional crosstalk in tumor progression pathways. The overexpression of ZWINT correlated with adverse clinical outcomes, showing 48% increased mortality risk (overall survival: HR 1.48, 95% CI 1.23-1.79), 66% higher recurrence probability (relapse-free survival: 1.66, 95% CI 1.50-1.84), and 63% elevated metastasis risk (distant metastasis-free survival: HR 1.63, 95% CI 1.39-1.90). Multivariate Cox regression incorporating TNM staging and molecular subtypes confirmed ZWINT as an independent prognostic determinant (P < 0.001, Harrell's C-index = 0.7827), which was validated through bootstrap resampling (1000 iterations).

Conclusion: ZWINT may serve as a potential biomarker for prognosis and a possible therapeutic target alongside TP53/CDH1 in breast cancer.

Objective: Acquired aplastic anemia (aAA) is characterized by an autologous immunological attack against hematopoietic stem and progenitor cells, and immunotolerance disruption is frequent, with reduced T regulatory cells (Tregs) frequencies and increased effector cytotoxic cells. Tregs are reduced in aAA and increase in number after successful immunosuppressive therapies.

Methods: In this retrospective study, we investigated the frequency of circulating Tregs by multiparametric flow cytometry immunophenotyping in non-severe aAA patients before and after immunosuppressive therapy. The samples were stained with the following antibodies: ECD anti-CD3, PE or PC5 anti-CD4, FITC anti-CD8, and PE anti-CD25, and Tregs were identified by first gating on linear parameters for lymphocyte identification and then for CD3 expression. In CD3⁺CD4⁺ cells, Tregs were further identified on the basis of CD25 and FOXP3 expression.

Results: Although the number of Tregs tended to increase after immunosuppressive treatments, their circulating frequency remained lower than that of healthy subjects, regardless of their responsiveness to therapies. Moreover, the relative frequency combined with absolute Treg counts might be more informative in the differential diagnosis of bone marrow failure syndromes.

Conclusions: The persistent decrease in circulating Tregs could be the result of immunosuppressive agents that could preferentially expand other T-cell subsets. At the same time, an imbalance in immunotolerance might persist, which is also favored by chronic antigen stimulation.

Objective: Schizophrenia is a complex neuropsychiatric disorder characterized by cognitive, affective, and behavioral abnormalities. Existing treatments have yielded limited effects on improving cognitive function. Recent studies have identified the abnormal differentiation of hippocampal neural stem cells (NSCs), neuronal loss, and dysregulated proliferation of astrocytes as significant pathological mechanisms contributing to the symptoms of schizophrenia. Impaired hippocampal neurogenesis may lead to emotional and cognitive deficits and biases in learning and memory, indicating that NSC differentiation is critical. NEP1-40, a Nogo-A receptor inhibitor, has shown promise for nerve protection and repair promotion. However, the effects of NEP1-40 on stem cell differentiation, the reduction in neuronal apoptosis, and the amelioration of schizophrenia-like behaviors have not been adequately investigated. This study examined the influence of NEP1-40 on NSC differentiation, hippocampal neuronal apoptosis, and proliferation in adolescent mice, along with its potential to enhance cognitive and behavioral outcomes in MK-801-induced schizophrenia mouse models.

Methods: In in vivo experiments, a schizophrenia mouse model was successfully established. Subsequently, behavioral tests were conducted, followed by Western blotting (WB) and immunofluorescence (IF) analyses. In in vitro settings, NSCs were cultured and transfected. Flow cytometry, along with WB and IF assays, was employed to evaluate the effects of NEP1-40.

Results: Schizophrenia-like behaviors in mice were significantly improved with the overexpression of NEP1-40. Compared with the model group, the NEP1-40 treatment group presented increased expression of a neuronal marker (Tuj1), reduced expression of an astroglial marker (GFAP), and decreased hippocampal neuronal apoptosis. NSC differentiation was assessed by quantifying the number of BrdU-positive cells coexpressing Tuj1 and GFAP in the hippocampal dentate gyrus. NEP1-40 treatment led to an increase in BrdU/Tuj1-positive cells and a reduction in BrdU/GFAP-positive cells. In cellular studies, NEP1-40 overexpression similarly increased the number of Tuj1-positive cells, reduced the number of GFAP-positive cells, decreased the degree of neuronal apoptosis, and promoted neuronal proliferation.

Conclusion: These findings demonstrated the neurogenic effects of NEP1-40 on NSCs and their potential to mitigate schizophrenia-like behaviors in vivo.

Background: Myocardial infarction (MI) and postmyocardial remodeling are the most common causes of heart failure worldwide and seriously affect the quality of life and prognosis of patients. Dapagliflozin, a sodium glucose cotransporter 2 (SGLT2) inhibitor, is a novel class of hypoglycemic drug that has been proven to have cardiovascular protective effects. However, the underlying mechanisms by which dapagliflozin affects MI have yet to be elucidated.

Methods: An MI mouse model was created by ligating the left anterior descending branch of the coronary artery. Hematoxylin‒eosin (HE) and Masson's trichrome (Masson) staining were used to assess myocardial damage. The levels of fibrosis-related and cuproptosis-related markers were assessed via Western blot analysis. A hypoxia-induced cardiomyocyte fibrosis model was constructed in vitro. The DCFH-DA probe was used to measure the levels of reactive oxygen species (ROS), and flow cytometry was used to identify cell apoptosis.

Results: Dapagliflozin improved heart function, ameliorated fibrosis in the myocardium, and alleviated myocardial injury. Moreover, dapagliflozin reduced the copper ion concentration and ROS accumulation and inhibited the expression of cuproptosis-related markers. Dapagliflozin suppressed the expression of HIF-1α/TGF-β signal and the overexpression of HIF-1α effectively reversed the dapagliflozin-mediated myocardial protective effects.

Conclusion: Dapagliflozin reduced myocardial fibrosis by suppressing HIF-1α/TGF-β-mediated cuproptosis.

Objective: This is a self-controlled multicenter retrospective study based on the clinical efficacy and complications of physiological reconstruction in the treatment of moderate and severe pelvic organ prolapse.

Methods: From December 2014 to August 2021, 517 women were included and registered for physiological reconstruction at four Chinese urogynecology institutions. We enrolled 364 women with POP-Q stage ≥ 3. The degree of POP was quantified via a POP-Q system. The surgical purpose of physiological reconstruction is to repair the vagina, levator ani muscle, perineum, and urogenital hiatus and adopt a repair method in accordance with the axial direction of physiology. All 330 evaluable participants were followed for 2 years. The evaluation indices included the PFDI-20, PGI-I, PFIQ-7, PISQ-12, PGI-I, and PGI-S. All complications were coded according to the category-time-site system proposed by the International Urogynecological Association (IUGA) and International Continence Society (ICS).

Results: Compared with the preoperative POP-Q scores, statistically significant improvements were observed at the 6-month, 1-year and 2-year time points (P < 0.001). Statistically significant improvements in quality of life were observed across all time points.

Conclusions: Physiologic reconstructive surgical techniques combined with modified anterior pelvic floor mesh implantation could help restore the physiologic axis and vaginal shape, which may be the most important factors in maintaining the functional position of pelvic floor organs and is the most effective method for repairing the pelvic fascia tendon arch. This surgical method is safe, feasible, and effective in patients with severe prolapse.

Objective: Numerous studies have established a link between hypertension (HTN) and a high-salt diet (HSD). However, the precise mechanisms are still being investigated, with increasing evidence suggesting that HSD can alter the gut microbiome balance, influence the production of microbiome metabolites and potentially lead to high blood pressure, presenting a promising avenue for targeting specific microbiota in HTN treatment. Short-chain fatty acids (SCFAs) are produced by gut bacteria and are associated with blood pressure regulation. Thus, the relationships among HSD, SCFAs, and blood pressure could provide valuable information on the pathophysiology of HTN. This study aimed to assess the impact of HSD on HTN by investigating its influence on the gut microbiota composition and SCFA levels in a rat model of HTN.

Methods: The HTN rat model was constructed by placing the rats on HSD (8% NaCl) for 8 weeks. On the 8th week, fecal samples were collected from the rats for DNA extraction. The profile of the gut microbiota was subsequently evaluated through 16S rRNA sequencing. The fecal SCFAs were subsequently measured and analyzed.

Results: Analysis of 16S rRNA sequencing data revealed that consumption of HSD was associated with an increase in pathogenic bacteria, including Turicibacter and Clostridia_UCG-014, and a decrease in beneficial bacteria, including Bifidobacterium and Lactobacillus. Metabolomic analysis of fecal samples suggested that HSD could increase the concentrations of most SCFAs, except caproic acid. Notably, a significant correlation was observed through Spearman correlation analysis between SCFAs and the changes in the gut microbiota caused by HSD, leading to a direct effect on SCFA levels.

Conclusion: The alterations in the gut microbiota resulting from HSD impact the levels of SCFAs, potentially disrupting gut equilibrium and initiating HTN, thereby increasing susceptibility to cardiovascular disease and associated health complications.

In recent years, adeno-associated viruses (AAVs) have emerged as leading vectors in gene therapy, with several FDA-approved treatments and ongoing clinical trials demonstrating their effectiveness in treating inherited retinal diseases, hemophilia, and Duchenne muscular dystrophy, among others. However, AAV-based therapies still face challenges, including immune responses and side effects, due to high viral doses. To address these challenges, various strategies have been developed, such as creating new viral capsids, optimizing gene expression regulation, and improving delivery methods. Localized delivery is a promising direction, utilizing the tissue tropism of AAVs to reduce systemic side effects and lower the required viral dose, thus improving targeting and efficiency, especially for organs that are difficult to treat with conventional methods. These innovations have opened new pathways for the clinical application of AAVs. This review aims to provide a comprehensive summary of the various applications of AAVs, offer valuable insights for future research directions, and holds significant importance for researchers and clinicians in the field. As AAV therapy continues to evolve, this article emphasizes its transformative potential in treating genetic diseases, indicating the central role of AAV in the future of gene therapy.

Objective: This study aimed to investigate the therapeutic effects and underlying mechanisms of the combination of Yinchenhao decoction (YCHD) and praziquantel (PZQ) in a Schistosoma japonicum (S. japonicum)-induced mouse model of schistosomiasis.

Methods: Six-week-old male BALB/c mice were randomly divided into five groups: control group, infected group, infected-PZQ group (I-PZQ), infected-YCHD group (I-YCHD), and infected-PZQ + YCHD group (I-PZQ + YCHD). The mice were infected with S. japonicum cercariae in infected group, I-PZQ group, I-YCHD group, and I-PZQ + YCHD group (n = 6 per group) and maintained for 63 days. From day 43 to day 63 postinfection, the mice received PZQ (150 mg/kg, intragastric gavage), YCHD (10 mL/kg, intragastric gavage), or a combination of both. The control and infected groups received equal amounts of sterile double-distilled water for the same period. At the end of the experiment, the mice were anesthetized with pentobarbital sodium and sacrificed. Serum alanine transaminase (ALT) and aspartate transaminase (AST) levels were measured. Network pharmacology analysis was used to predict the targets of YCHD in the treatment of schistosomiasis. Histopathological analysis, Western blotting, immunofluorescence, quantitative polymerase chain reaction and flow cytometry were employed to evaluate liver pathology and molecular changes.

Results: Compared with the other groups, the I-PZQ + YCHD group presented significantly decreased serum ALT and AST levels (P < 0.001). The I-PZQ + YCHD group exhibited improved pathological changes in the liver, as evidenced by reduced area of single granuloma (P < 0.01), granuloma area (P < 0.01), and Ishak score of liver fibrosis (P < 0.01). Network pharmacology analysis suggested that YCHD may alleviate schistosomiasis-related liver injury through the modulation of the endoplasmic reticulum stress (ERS) pathway. Western blot analysis revealed that ERS-related markers, including glucose-regulated protein 78 (GRP78), inositol-requiring enzyme 1 alpha (IRE1α), X-box binding protein 1 (XBP-1), and C/EBP homologous protein (CHOP), were significantly downregulated in the I-PZQ + YCHD group (P < 0.05). Furthermore, the I-PZQ + YCHD group presented reduced hepatocyte apoptosis (P < 0.05), diminished hepatic macrophage infiltration (P < 0.05) and downregulated expression of proinflammatory cytokines (TNF-α, IL-1β and IL-6) (P < 0.05).

Conclusion: YCHD combined with PZQ reduced schistosomiasis-associated hepatic granulomatous inflammation and fibrosis by inhibiting hepatic apoptosis and ERS.